An important tool to estimate the detrimental effect of a variant is represented by the Combined Annotation Dependent Depletion score (C-score).106 This score combines different information, such as the variant consequence on DNA gene sequence, its impact on expression, acetylation, and methylation, and the conservation score of the region, in a single metric. The higher the C-score, the more deleterious is the variant; to identify potentially pathogenic variants, Kircher and colleagues suggested using a cut-off value between 10 and 20. In this way, the C-scores give important information about the different allelic impact of a variant, its functional role and pathogenicity; also allowing to rank causal variants in a genome sequence. We calculated the C-score for UTR variants in the GWAS Catalog data and obtained values ranging from 0.001 to 22.1, with a relatively low mean value (mean=5.89), indicating that variants in UTRs are mainly benign. We then prioritized only those variants unequivocally mapping in UTRs from VEP annotation (table 5). Among the most deleterious variant, rs1128334 (C-score = 16.2) was notable in that it was associated with systemic lupus
